Clinical significance of R‐wave amplitude in lead V1 and inferobasal myocardial infarction in patients with inferior wall myocardial infarction

Abstract Objective To assess electrocardiogram (ECG) for risk stratification in inferior ST‐elevation myocardial infarction (STEMI) patients within 24 h. Methods Three hundred thirty‐four patients were divided into four ECG‐based groups: Group A: R V1 <0.3 mV with ST‐segment elevation (ST↑) V7–V9, Group B: R V1 <0.3 mV without ST↑ V7–V9, Group C: R V1 ≥0.3 mV with ST↑ V7–V9, and Group D: R V1 ≥0.3 mV without ST↑ V7–V9. Results Group A demonstrated the longest QRS duration, followed by Groups B, C, and D. ECG signs for right ventricle (RV) infarction were more common in Groups A and B (p < .01). ST elevation in V6, indicative of left ventricle (LV) lateral injury, was more higher in Group C than in Group A, while the ∑ST↑ V3R + V4R + V5R, representing RV infarction, showed the opposite trend (p < .05). The estimated LV infarct size from ECG was similar between Groups A and C, yet Group A had higher creatine kinase MB isoform (CK‐MB; p < .05). Cardiac troponin I (cTNI) was higher in Groups A and C than in B and D (p < .05 and p = .16, respectively). NT‐proBNP decreased across groups (p = .20), with the highest left ventricular ejection fraction (LVEF) observed in Group D (p < .05). Group A notably demonstrated more cardiac dysfunction within 4 h post‐onset. Conclusions For inferior STEMI patients, concurrent R V1 <0.3 mV with ST↑ V7–V9 suggests prolonged ventricular activation and notable myocardial damage. RV infarction's dominance over LV lateral injury might explain these observations.

STEMI, a pathological Q wave on the ECG prior to reperfusion is commonly noted.The prevalence of Q wave during the thrombolytic therapy era was between 33% and 53%, and during the percutaneous coronary intervention (PCI) era, it was between 21% and 72% (Andrews et al., 2000;Armstrong et al., 2009;Raitt et al., 1995;Topal et al., 2017Topal et al., , 2020)).Notably, in STEMI, an abnormal Q wave might not conclusively indicate irreversible myocardial damage.It could signify intense, yet reversible, cellular ischemia or depict stunned and hibernating myocardium (Bateman et al., 1983;Sztajzel & Urban, 2000).Even though a baseline Q wave suggests a poor prognosis, STEMI patients with a Q wave still gain advantages from primary PCI (Topal et al., 2017), and effective reperfusion therapy can lead to Q-wave regression or the return of R wave from hours to weeks post-STEMI, hinting at recovered myocardial and improved left ventricular functions (Rijnierse et al., 2012;Sztajzel & Urban, 2000).
In the chronic phase of inferior STEMI, a pronounced R wave in lead V 1 is indicative of left ventricle (LV) lateral wall myocardial necrosis, often seen as a "pathological R wave" mirror reflecting the lateral wall Q wave (Bayés de Luna et al., 2015).It is worth noting that even without an infarction, significant myocardial ischemia can produce early QRS changes.Our clinical observations confirm that some patients with an inferior myocardial infarction (IMI) present an obvious R wave in lead V 1 shortly after onset, and moreover, an accentuated R wave during the acute phase may evolve into a more conspicuous R wave as the condition becomes chronic.This observation has led us to speculate that a significant R wave in lead V 1 could be indicative of substantial lateral wall myocardial injury in cases of IMI.
Additionally, right ventricular myocardial infarction (RVMI) can induce QRS alterations in the precordial leads (Halkett et al., 1986;Roesler & Dressler, 1947).Given the anatomical positioning of the right ventricle (RV) against the lateral wall of LV and based on ECG vector cancellation theory, RVMI can potentially offset the ischemic vector from the lateral wall.Thus, the presence of RVMI might suppress the R-wave amplitude in lead V 1 , possibly masking the lateral myocardial damage.
ST-segment elevation (ST↑) in leads V 7 -V 9 suggests a concurrent inferobasal myocardial infarction (IBMI), implying a greater myocardial injury (Adawi & Atar, 2008).And a prolonged QRS duration (QRSd), caused by widespread ischemia from multivessel disease, is also a predictor of worse outcomes in AMI patients (Shah et al., 2016).Consequently, this study seeks to explore the implications of R-wave amplitude in lead V 1 , ST-segment patterns in posterior chest leads, and their impact on QRSd.The goal is to refine our understanding of the ECG's utility in stratifying risks for patients diagnosed with inferior STEMI.

| Study population
This retrospective study at Shanxi Cardiovascular Hospital involved 334 patients with acute inferior STEMI, defined in accordance with the Fourth Universal Definition of Myocardial Infarction, including elevated cardiac troponin I (cTNI) levels, symptoms of myocardial ischemia, and new ST↑ in the inferior ECG leads.(Thygesen et al., 2018).
The patients undergoing emergency coronary angiography were included from January 2019 to August 2021 and May 2023 to August 2023 to maintain sample size (Figure 1a).Reperfusion within 12 h is more beneficial, but guidelines suggest extending the window to 24 h is also viable, so our criteria include up to 24 h (Lawton et al., 2022).
Clinical data and in-hospital outcomes were extracted from electronic medical records, selecting the peak levels of cardiac enzymes and troponin during their stay.Exclusions included patients with: (1) concurrent acute anterior STEMI or those with the left anterior descending (LAD) artery as the culprit vessel, (2) other heart conditions such as myocarditis, pericarditis, cardiomyopathy, congenital heart diseases, or variant angina, and (3) those on oral antiarrhythmic drugs (classes I, III, and IV), those with persistent bundle branch block, or those with a complete pacemaker rhythm.

| ECG grouping and diagnostic criteria
The first ECG after admission to the emergency department and before PCI was selected.The ECG was recorded with the standard 12 leads and the right precordial chest leads V 3 R-V 5 R and the posterior chest leas V 7 -V 9 at a paper speed of 25 mm/s and an amplification of 10 mm/mV.Based on the R-wave amplitude in lead V 1 and the presence or absence of ST↑ in posterior leads, the patients were divided into four groups: Group A: R V 1 <0.3 mV with ST↑ V 7 -V 9 , Group B: R V 1 <0.3 mV without ST↑ V 7 -V 9 , Group C: R V 1 ≥0.3 mV with ST↑ V 7 -V 9 , and Group D: R V 1 ≥0.3 mV without ST↑ V 7 -V 9 (Figure 1b).Among them, R V 1 ≥0.3 mV in IMI represents lateral myocardial involvement (Goldwasser et al., 2015).The magnitude of ST-segment deviation relative to the TP-segment was measured at the J-point in all leads.ST↑ >0.1 mV in two of the inferior leads was diagnosed as IMI.ST↑ >0.05 mV in leads V 3 R-V 5 R was diagnosed as RVMI, also the other signs for RVMI including QS or QR in leads V 3 R-V 5 R, QS in lead V 1 and simultaneous ST↑ in lead V 1 , and depression in lead V 2 were evaluated (Coma-Canella et al., 1986;Mak et al., 1994;Morgera et al., 1984).The IBMI was diagnosed by ST↑ >0.05 mV in leads V 7 -V 9 .The diagnostic cut-off value was based on the electrocardiographic content of the Fourth Universal Definition of Myocardial Infarction (Thygesen et al., 2018).The LV infarcted size, expressed as a percentage of LV mass, can be computed using the modified Aldrich score = 3 × (0.6 (∑ST↑ II, III, aVF) + 2.0) + 3 × (1.5 (number of other leads with ST↑) − 0.4) (Clemmensen et al., 1991).The early Q wave before reperfusion defined as Q duration ≥40 ms and depth ≥25% of the R and the Sclarovsky-Birnbaum Ischemia Grade was recorded in lead III (Topal et al., 2017).The Sclarovsky-Birnbaum Ischemia Grading System (SB-IG) is an electrocardiographic method evaluating the severity of ischemia based on QRS-ST-T changes, but inverted or biphasic T is excluded (Billgren et al., 2004).Ventricular arrhythmias included frequent ventricular premature beats, paroxysmal ventricular tachycardia, and ventricular fibrillation.

| Coronary angiography
Coronary artery stenosis was assessed by at least two experienced interventional cardiologists using multiangle projections from a multifunctional angiography catheter, accessed via the radial or femoral artery.The left main (LM) coronary artery or LAD artery disease was defined as >50% stenosis.Triple vessel disease was defined as >50% stenosis in the LAD artery, left circumflex (LCX) artery, and right coronary artery (RCA).Thrombolysis in myocardial infarction (TIMI) grades related to prognosis are defined as: 0, 1, 2, 3 = no, minimal, partial, normal flow respectively.TIMI 0-1 = effective occlusion (GUSTO Angiographic Investigators, 1993;Simes et al., 1995).

| Statistical analysis
We employed IBM SPSS 22.0 for statistical analysis and data processing.Continuous variables were represented as mean ± standard deviation, and comparisons between groups were conducted using the t-test.The times from symptom onset to ECG recording and angiography, as well as from door to wire through, were expressed as medians with interquartile ranges.Group comparisons were conducted using the Kruskal-Wallis test.Categorical data were presented as percentages or ratios, and comparisons were made using the chi-squared test or Fisher's exact test.A p-value less than .05was deemed statistically significant.

| Basic demographic characteristics, myocardial injury markers, and in-hospital prognosis
The age in Groups A and B was older than that in Group C, and glucose in Groups A and B was higher than that in the other two groups (p < .05).Group A had the highest creatine kinase MB isoform (CK-MB) levels among four groups (p < .05).Both Groups A and C showed elevated cTNI compared to Groups B and D (p < .05 and p = .16,respectively).N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels decreased sequentially across the groups (p = .20),with Group D having the highest left ventricular ejection fraction (LVEF) (p < .05)(Figure 2).There were no statistically significant differences in gender, disease spectrum, or serum biochemical parameters and arrhythmia, cardiogenic shock, or death among the four groups (all p > .05)(Table 1).

| Coronary angiographic findings
In Groups A and B, the culprit lesions were predominantly in the proximal or middle RCA.In Group C, they were frequently in the distal RCA or the proximal and middle LCX.In Group D, lesions were mainly in the distal segment of both the RCA and LCX (all p < .05).
The initial TIMI blood flow grade, LAD disease, LM disease, and triple vessel disease showed no statistically significant difference across the four groups (Table 2).

| ECG parameters
Our results showed that QRSd in Group A > Group B > Group C > Group D (p < .05)(Figure 3).Among the four groups, the proportion of SB-IG II and Q wave was lowest in Group D (Figure 4).The proportions of RVMI indicators in Groups A and B were significantly higher than those in groups C and D (p < .01).IBMI was significantly associated with a greater sum of ST↑ in inferior leads and LV infarcted size.
The extent of LV lateral injury is largest in Group C because of the highest ST↑ elevation in lead V 6 (Table 3).

<4 h
In 144 patients with inferior STEMI within 4 h, Group A showed the highest cTNI, CK-MB, and NT-proBNP, and the lowest LVEF, with significant differences only versus Group D (p < .05).Group A also had the most patients with SB-IG III among all groups (p < .05)(Table 4).

| DISCUSS ION
Similar to the significance of the early "pathological Q wave" in STEMI, the "pathological R wave" in lead V 1 presumably represent severe lateral injury in inferior STEMI's acute phase, but the R-wave amplitude can be offset by right ventricular infarction.Our study highlights a patient subgroup with larger infarct sizes, marked by an R wave <0.3 mV in lead V 1 and ST↑ in leads V 7 -V 9 .(2) However, it is crucial to note that ECG changes in the right thoracic leads are influenced by the combined electrical activities of both the RV and the lateral wall of left ventricle (LV) (Lew et al., 1985;Mukharji et al., 1984).Roeslerb et al. conducted autopsies on five IMI patients exhibiting reduced Q-or Rwave amplitude in right precordial leads.Their findings revealed interventricular septal necrosis extending from the anterior to the posterior regions.In some instances, there was concurrent myocardial necrosis in the adjacent septum (Roesler & Dressler, 1947).

| QRS wave morphology in lead V 1 is affected by multiple infarct regions
Subsequently, Halkett and Khan documented six IMI patients with ST↑ in leads V 1 -V 3 /V 4 and a QS or rS waveform.Ventriculography or cardiac color Doppler ultrasound highlighted RV dilatation or diminished RV functionality.Meanwhile, the LV wall and interventricular septum remained functional.Coronary angiography affirmed RCA occlusion, yet the LAD artery remained patent.Their conclusion was clear: the necrotic Q wave in leads V 1 -V 3 was not indicative of anterior septal or anterior wall myocardial infarction but was a manifestation of RV infarction (Halkett et al., 1986;Khan & Chou, 1996).
(3) Advances in cardiac imaging have shown that leads V 1 -V 3 are associated with the heart's inferior (posterior) septal segment.A Q wave in V 1 signifies myocardial perfusion defects in the infero-septum of LV basal segment (Jia et al., 2018;Zafrir et al., 2004).

| Differential diagnosis of QS wave in lead V 1
QS waves in lead V 1 are commonly observed in various scenarios: septal myocardial scarring of nonischemic etiology (Ghadban et al., 2018); isolated septal myocardial infarction (Harimoto et al., 2019;Tomcsanyi et al., 2012); and anterior or apical myocardial infarction (Allencherril et al., 2018;Bogaty et al., 2002).It is rarely that a decrease in R-wave amplitude or the presence of Q waves in lead V 1 is attributed clinically to RV myocardial injury.However, theoretically, this association is feasible, as supported by autopsy findings (Lopez-Sendon et al., 1985).Some cases have also reported isolated RV or RV outflow tract infarctions, visible on CMRI, being attributed to nondominant RCA or conal branch occlusion.These events can reduce the R-wave amplitude in lead V 1 and even produce pathological Q waves in leads V 2 and V 3 (Halkett et al., 1986;Khan & Chou, 1996;Lyle et al., 2016;Zhong et al., 2019).Furthermore, a Qr or QR morphology in lead V 1 during acute pulmonary embolism is linked with increased RV stress (Kucher et al., 2003).This is attributed to RV myocardial injury and is seen as an indicator of RV insufficiency.Notably, such patients have a 3.62-fold increased risk of cardiogenic shock (Kukla et al., 2014).All these findings may lend support to our speculation.

| Probable mechanism decreasing R wave of lead V 1 in inferior myocardial infarction
Consequently, the R-wave amplitude in lead V 1 is influenced by myocardial infarction in both the LV lateral wall and the RV, among other sites.During an episode of IMI, the diminished R wave, or the shift to rS or even QS patterns in lead V 1 , is presumably due to a deficiency in the normal left-to-right depolarization vector caused by the RV free wall.
Even when the lateral wall is involved, R V 1 >0.3 mV may not appear on the ECG at this juncture.This is because the right-to-left infarction force from the RV is predominant, which counterbalances the left-toright infarction vector from the LV lateral wall.Consequently, the composite vector deviates from lead V 1 , diminishing the R-wave amplitude in this lead.We postulate that this hypothesis explains the reduced sensitivity and negative predictive value of R V1 >0.3 mV in diagnosing lateral wall involvement, particularly when encompassing acute-phase IMI patients and expanding the sample size (45 vs. 155 patients with Comparisons of percent of SB-IG, inverted or biphasic T and early Q among four groups.Group A: R V 1 <0.3 mV with ST↑ V 7 -V 9 , Group B: R V 1 <0.3 mV without ST↑ V 7 -V 9 , Group C: R V 1 ≥0.3 mV with ST↑ V 7 -V 9 , Group D: R V 1 ≥0.3 mV without ST↑ V 7 -V 9 .SB-IG, Sclarovsky-Birnbaum Ischemia Grading System. inferior and lateral wall myocardial infarction, the sensitivity and negative predictive values were 73.4% vs. 27.7%, and 63.6% vs. 41.6%,respectively) (Goldwasser et al., 2015).Additionally, the incidence of the proximal RCA being the culprit artery was higher in patients in Groups A and B than in Groups C and D. The obstruction of this proximal segment diminishes the blood supply from the posterior descending artery to the lower (posterior) septal.The resultant ischemia further weakens the R wave in lead V 1 .
The ST↑ magnitude correlates with the extent of myocardial injury (Hathaway et al., 1998).Studies have indicated that the sum of absolute ST-segment deviations can predict patient prognosis.
Based on this, in our study, we hypothesized that the severity of myocardial injury or infarction in STEMI patients can be partly inferred from the acute ∑ST↑ in ECGs recorded before reperfusion therapy.We interpret ∑ST↑ II + III + aVF, ∑ST↑ V 7 + V 8 + V 9 , and as indications of inferior, inferobasal, and right wall myocardial injury or infarction, respectively.Additionally, ST↑ in V 6 indicates lateral involvement in the acute phase of inferior STEMI (Norda et al., 2015).We, therefore, consider ST↑ V 6 as a marker of lateral injury extent.Notably, patients in Group C exhibit a larger lateral injury extent than those in Group A, yet the LV infarcted sizes, estimated by the modified Aldrich score, are comparable between both groups.However, the total infarcted extent, as estimated by serum markers, is higher in Group A. This discrepancy suggests that the more extensive myocardial injury in Group A may result from a significant right ventricular Compared with Group C, a p < .05,compared with Group D, b p < .05,compared with Group B, c p < .05.
involvement, as evidenced by the higher ∑ST↑ V 3 R + V 4 R + V 5 R in Group A compared to Group C. The explanation is particularly relevant for inferior STEMI >4 h, given that the necrotic extent, estimated by CK-MB or cTNI, is similar in those <4 h in both Groups A and C.However, in early-onset patients (<4 h) with additional ST elevation in leads V 7 -V 9 , the R V 1 <3 mm suggests worse left heart function.This is indicated by higher NT-proBNP (p = .377)and lower LVEF (p = .286)in Group A, likely due to RVMI impairing left ventricular filling (Nägele & Flammer, 2022) and more limited collateral circulation in the LV itself, evidenced by the fact that more patients in Group A presented with severe ischemia (SB-IG III) (Billgren et al., 2004).
4.4 | ST↑ in leads V 7 -V 9 denotes a more severe ischemic event than its absence in inferior myocardial infarction Matetzky S et al. demonstrated that ST↑ in leads V 7 -V 9 signifies abnormalities in the motion of the inferior or inferolateral wall of the basal segment, as evidenced by echocardiography.Therefore, in our study, the term "inferobasal myocardial infarction (IBMI)" is used to denote the ST↑ in V 7 -V 9 , a terminology that aligns with the fourth definition of myocardial infarction.Roughly 53% of patients with IMI present with IBMI, with the responsible artery being either the RCA, LCX, or their branches.It is noteworthy that patients diagnosed with both IMI and IBMI exhibit a heightened incidence of congestive heart failure, reinfarction, mortality, and mitral regurgitation compared to those without IBMI.The extent of the infarct in such cases is comparable to that observed in anterior MI.Additionally, these patients are more likely to derive significant benefits from revascularization therapy (Adawi & Atar, 2008;Matetzky et al., 1998).In our Groups A and C, patients with concurrent IBMI exhibited higher cTNI levels compared to Groups B and D without IBMI.Group D patients demonstrated a superior LVEF, suggesting a more extensive myocardial damage and compromised LV systolic function when paired with IBMI.Although Groups A and B saw a heightened prevalence of cardiogenic shock, there was not a significant statistical difference, as well as in NT-proBNP trends among the groups.This could be attributed to the mitigative effects of timely PCI in preventing complications for some patients.

| Implications of prolonged QRS duration in myocardial infarction
Our study indicated a progressive shortening of the QRSd from Group A to D, with the longest duration observed when R V 1  *LV infarcted size expressed by a percentage of the LV mass was calculated using the modified Aldrich score = 3 × (0.6 (∑ST↑ II, III, aVF) + 2.0) + 3 × (1.5 (no. of other leads with ST↑) − 0.4).

| LI M ITATI O N S
There are some limitations to this study.Firstly, the sample size of "R V1 ≥0.3 mV without IBMI" in Group D was too small, probably because the pathological R wave in lead V 1 predict the "(aterolateral) lateral wall" injury, and the ST↑ in the V 7 -V 9 leads represents inferior basal or partly the posterior lateral wall (Sclarovsky et al., 1987)

| CON CLUS ION
We identified a high-risk subset of patients with inferior myocardial infarction, characterized by a decreased R-wave amplitude in lead V 1 and ST↑ in leads V 7 -V 9 .A potential underlying mechanism is the greater infarct size in the right ventricle compared to the lateral wall of the left ventricle, with the inferobasal wall area also affected.
Such patients exhibit prolonged QRS duration, most indicative of compromised cardiac function within 4 h post-inferior STEMI, yet they benefit significantly from interventional treatments in the widespread adoption of PCI.

F
Flow chart of patient inclusion (a) and the ECG examples in four groups (b).
Approximately two-thirds of patients with inferior myocardial infarction (IMI) present with a lateral wall myocardial infarction.The QRS waveform change in lead V 1 can be influenced by myocardial necrosis in different regions.(1) de Luna et al. revealed that the electrocardiographic activity of the lateral wall can be represented F I G U R E 2 Comparisons of mean values of serum cTNI, CK-MB, and NT-proBNP among four groups.Group A Compared with Group C, a p < .05,compared with Group D, b p < .05,compared with Group B, c p < .05.CK-MB, creatine kinase MB isoform; cTNI, cardiac troponin I; NT-proBNP, N-terminal pro-B-type natriuretic peptide.
, above infarcted positions are adjacent, hence the coexistence of those is common.Secondly, complete ST-segment resolution post-PCI indicates successful reperfusion, while Q-wave regression implies enhanced LV function.However, the lack of postreperfusion ST-segment recovery and ECG follow-up, their prognostic value in our groups is undetermined.Thirdly, approximately 18% of our patients were treated after 12 h, missing the optimal reperfusion window, and the fact that only 43.1% arrived within 4 h limits comparison with other studies such as Andrews et al. included only patients presenting at <4 h.Yet, despite the time-related variability in myocardial infarction severity, our findings provide a potential explanation.Lastly, post-PCI, our center enforces a 3-month waiting period before conducting CMRI to mitigate stent-related concerns, despite evidence support that early CMRI in AMI patients is safe and not posing potential risks.Hence, patients also did not undergo CMRI to clarify the specific infarct site or area at risk in the acute phase.Large-scale studies combining the imaging evaluation and time-dependent ECG stratification are needed to further test our proposition.
Comparisons of clinical data, myocardial injury marker and in-hospital prognosis among four groups (x ± s, medians and interquartile range, or %).
TA B L E 1 Comparisons of angiographic and procedural findings among four groups (x ± s, medians and interquartile range, or %).
Compared with Group C, a p < .05,comparedwithGroupD, b p < .05,comparedwithGroupB, c p < .05.Abbreviations: CK-MB, creatine kinase MB isoform; cTNI, cardiac troponin I; LVEF, left ventricular ejection fraction; NT-proBNP, N-terminal pro-Btype natriuretic peptide.*Drinking is defined as consuming eight standard drinks per week, each containing about 14 g of pure alcohol.†Detectedby Kruskal-Wallis test.TA B L E 2 Comparisons of ECG parameters among four groups (x ± s or %).
TA B L E 3 Comparisons of clinical data and ECG parameters among four groups in patients presenting<4 h (x ± s or %).
<0.3 mV was combined with IBMI.We speculate this is due to: (1) under hypoxia and acidosis with sodium-potassium pump inhibition or potassium ATP channel activation, localized hyperkalemia slows conduction in ischemic areas.The larger the ischemic area, as seen in Group A patients, often with concurrent RV and TA B L E 4 Compared with Group C, a Abbreviations: RVMI, right ventricular myocardial infarction; SB-IG, Sclarovsky-Birnbaum Ischemia Grading System.
, especially the former is prominent in the hyperacute stage (<4 h), as equally longer QRSd in both Groups A and C with ST elevation in posterior leads.However, Escobar et al., 2022).In non-STEMI patients, Shah M et al. identified that a QRSd ≥90 ms indicates significant coronary artery involvement